In vitro antiherpetic activity of water-soluble amphotericin B methyl ester

Stevens, N. M.; Engle, Claire G.; Fisher, Paul B.; Mechlinski, Witold; Schaffner, Carl P.

doi:10.1007/bf01317438

Cited by 28 publications

(17 citation statements)

References 3 publications

(1 reference statement)

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“…Variation of the inoculum size over a wide range did not systematically affect the percentage of VSV inhibited by AME. These results differ in some respects from the findings of Stevens et al (11), who studied the inactivation of several strains of herpes simplex by AME. They also observed a wide variation in the susceptibilities of different strains of herpesvirus, which may, in part, be responsible for the differences reported here.…”

Section: Discussioncontrasting

confidence: 56%

“…In contrast, the methyl ester of amphotericin B (AME) is water soluble and less toxic and retains antifungal activity (3,8). Recently, activity of AME against herpesviruses has been reported (11). We describe the binding of AME to vesicular stomatitis virus (VSV), the kinetics of the antiviral action, and the spectrum of activity against several classes of enveloped and unenveloped viruses.…”

mentioning

confidence: 99%

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Antiviral Effects of Amphotericin B Methyl Ester

Jordan

Seet

1978

Antimicrob Agents Chemother

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The methyl ester of amphotericin B (AME) is water soluble, retains antifungal activity, and is significantly less toxic in mammals than amphotericin B. In contrast to amphotericin B, which is not water soluble, AME exhibits antiviral effects against vesicular stomatitis virus, herpes simplex virus types 1 and 2, Sindbis virus, and vaccinia virus in a plaque reduction assay. No antiviral effects could be demonstrated against the unenveloped adenovirus type 4 or echovirus type 11. The extent of virus inactivation was found to be dependent upon the AME concentration, contact time, and temperature. No consistent effect of the virus concentration on the probability of plaque-forming unit inactivation could be determined. The antiviral effects of AME were partially antagonized by the presence of serum. Binding of AME to vesicular stomatitis virus was demonstrated by the comigration of drug and virus in linear sucrose gradients. AME represents a new class of antiviral agents with activity at concentrations relevant to therapeutics. Sterol components of the host cell membrane that become incorporated into the viral envelope are postulated as the site of reaction with AME.Amphotericin B is a polyene macrolide antimicrobical agent that is currently the most effective agent available for the treatment of many systemic fungal infections in man. The biological properties of the polyenes result primarily from interaction with sterol components of the cell membrane (6). The major disadvantages of amphotericin B are its poor solubility in water, necessitating stabilization of suspensions with deoxycholate, and its numerous toxic side effects. In contrast, the methyl ester of amphotericin B (AME) is water soluble and less toxic and retains antifungal activity (3,8). Recently, activity of AME against herpesviruses has been reported (11). We describe the binding of AME to vesicular stomatitis virus (VSV), the kinetics of the antiviral action, and the spectrum of activity against several classes of enveloped and unenveloped viruses. MATERLALS AND METHODSReagents. Cells were grown in Eagle basal medium with 10% fetal bovine serum (FBS). Maintenance medium consisted of Eagle basal medium with 2% FBS. Gentamicin (10 ug/ml) was added to all media. Hanks balanced salt solution with 0.5% gelatin, but no serum, was used for the dilution of viruses and AME.The hydrochloride of AME was kindly supplied, as a yellow, dry powder, by Carl P. Schaffner, The Waksman Institute of Microbiology, Rutgers University, New Brunswick, N.J. Tritiated AME had a specific activity of 1.2 x 106 dpm/mg. One-half-milliliter portions of a stock solution of AME in sterile distilled water (2 mg/ml) were frozen at -70°C; no turbidity or precipitation was observed.

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Section: Discussioncontrasting

confidence: 56%

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confidence: 99%

Antiviral Effects of Amphotericin B Methyl Ester

Jordan

Seet

1978

Antimicrob Agents Chemother

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“…AmB and its water-soluble derivative Amb methyl ester have also been shown to have antiviral properties against several different groups of enveloped viruses (11,14,24). Structurally, hepatitis B virus (HBV) is similar to other lipidenveloped viruses in that it has an inner nucleocapsid surrounded by an outer lipoprotein envelope which has hepatitis B surface antigen (HBsAg)-reactive determinants (21).…”

mentioning

confidence: 99%

Effects of amphotericin B on hepatitis B virus

Kessler¹,

Dixon²,

Howard³

et al. 1981

Antimicrob Agents Chemother

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We investigated the effects of amphotericin B (AmB) on the ultrastructure and biochemistry of hepatitis B virus (HBV) core component possesses an immunologically distinct hepatitis B core antigen (HBcAg) reactivity which on further disruption reveals the third HBV-associated antigen, hepatitis B e antigen (21). Also present in the sera of infected individuals are 22-nm HBsAg particles, which have been shown by biochemical analysis to contain approximately 23% lipid by dry weight in addition to protein and carbohydrates (25). Neutral lipids account for 22.3% of this fraction, with 59% of these being cholesterol and cholesterol esters (25). We predicted, therefore, that AmB would have an effect on the structural integrity of HBV particles, assuming the outer lipid membrane to be of approximately the same chemical composition as HBsAg particles. This study was therefore undertaken to determine the ultrastructural effects of AmB on HBV and the 22-nm form of HBsAg as determined by HBV deoxyribonucleic acid (DNA) polymerase activity, electron microscopy (EM), differential ultracentrifugation, and sucrose density centrifugation.MATERIALS AND METHODS HBV and HBsAg. Partially purified HBV and purified 22-nm HBsAg particles were obtained as previously described from a chimpanzee chronically infected with HBV (10, 22). Radioiodinated purified HBsAg particles were prepared as described by Skelly et al. (23). HBV-associated DNA polymerase activity was determined by the method of Howard (9)

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“…Both drugs reduce the infection of lymphocytes by human immunodeficiency virus type 1 (HIV-1), the aetiological agent of AIDS. They influence a variety of enveloped RNA and DNA viruses by complexing membrane cholesterol, an event that causes changes in cell permeability and function and results in a significant resistance to virus replication (Schaffner et al, 1986;Stevens et al, 1975).…”

Section: Discussionmentioning

confidence: 99%

Lauric acid inhibits the maturation of vesicular stomatitis virus

Hornung

Amtmann

Sauer

1994

Journal of General Virology

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In the presence of lauric acid (C12), the production of infectious vesicular stomatitis virus (VSV) was inhibited in a dose-dependent manner. The inhibitory effect was reversible: after removal of C12 the antiviral effect disappeared. In addition, the chain length of the monocarboxylic acids proved to be crucial, as those with shorter or longer chains were less effective or had no antiviral activity. Concomitant with the C12-induced inhibition was the stimulation of triacylglycerol synthesis, increasing the amount up to ninefold. Analysis of the antiviral mechanism of C 12 revealed that the correct assembly of the viral components was disturbed, but viral RNA and protein synthesis remained unimpaired.By cell fractionation and Western blot analysis the amount of viral M protein located in the plasma membrane was found to be markedly reduced after treatment with C12, whereas in the cytoplasm the quantity of M protein was similar to that in untreated cells. C12 did not influence M protein synthesis, but prevented the binding of M protein to the host cell membrane, where the protein plays an essential role in virus assembly. Thus, treatment of VSV-infected cells with C12 resulted in inhibition of virus release. It is suggested that the newly synthesized triacylglycerols might interact with the host cell plasma membrane and interfere with virus maturation.

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In vitro antiherpetic activity of water-soluble amphotericin B methyl ester

Cited by 28 publications

References 3 publications

Antiviral Effects of Amphotericin B Methyl Ester

Antiviral Effects of Amphotericin B Methyl Ester

Effects of amphotericin B on hepatitis B virus

Lauric acid inhibits the maturation of vesicular stomatitis virus

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